{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T05:09:43Z","timestamp":1778389783653,"version":"3.51.4"},"reference-count":160,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aging profoundly alters hematopoiesis by impairing stem cell self-renewal, skewing lineage differentiation, and remodeling immune and stromal compartments within the bone marrow. Consequently, these changes contribute to an increased susceptibility to leukemia. Conversely, leukemia contributes to systemic aging. Although the connection between hematopoietic aging and leukemogenesis has been well-recognized, the precise molecular and microenvironmental mechanisms underlying this association remain poorly elucidated. In recent years, emerging studies have identified altered clonal dynamics, chronic inflammation, and niche-dependent metabolic remodeling as major contributors to malignant transformation. Building on these findings, we synthesize current insights into how aging reprograms the hematopoietic ecosystem to promote leukemic initiation and progression, and furthermore, discuss potential strategies to counteract these processes by targeting aging-related pathways.<\/jats:p>","DOI":"10.3390\/ijms27094043","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T14:35:53Z","timestamp":1777559753000},"page":"4043","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hematopoietic Aging and Leukemia: Mechanistic and Therapeutic Insights"],"prefix":"10.3390","volume":"27","author":[{"given":"Zhihui","family":"Li","sequence":"first","affiliation":[{"name":"Department of Hematology and Oncology, Shanghai Children\u2019s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200062, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4364-6624","authenticated-orcid":false,"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Medical Center on Aging of Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2614-8682","authenticated-orcid":false,"given":"Nuo","family":"Cheng","sequence":"additional","affiliation":[{"name":"Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Shanghai Children\u2019s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200062, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoling","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medical Center, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingbo","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Shanghai Children\u2019s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200062, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"Blasco","year":"2013","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"102264","DOI":"10.1016\/j.xcrm.2025.102264","article-title":"Cardiovascular inflammaging: Mechanisms, consequences, and therapeutic perspectives","volume":"6","author":"Spray","year":"2025","journal-title":"Cell Rep. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/s41392-025-02346-0","article-title":"Arterial stiffness and vascular aging: Mechanisms, prevention, and therapy","volume":"10","author":"Herzog","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.1038\/s41591-025-03798-1","article-title":"Plasma proteomics links brain and immune system aging with healthspan and longevity","volume":"31","author":"Oh","year":"2025","journal-title":"Nat. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s13073-025-01501-0","article-title":"Developing a novel aging assessment model to uncover heterogeneity in organ aging and screening of aging-related drugs","volume":"17","author":"Xu","year":"2025","journal-title":"Genome Med."},{"key":"ref_6","first-page":"12","article-title":"The ageing gastrointestinal tract","volume":"19","author":"Soenen","year":"2016","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"101151","DOI":"10.1016\/j.arr.2020.101151","article-title":"The ageing kidney: Molecular mechanisms and clinical implications","volume":"63","author":"Fang","year":"2020","journal-title":"Ageing Res. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1182\/blood.2022017933","article-title":"Hematopoietic stem cell aging and leukemia transformation","volume":"142","author":"Mistry","year":"2023","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"38","DOI":"10.3324\/haematol.2018.211334","article-title":"Microenvironmental contributions to hematopoietic stem cell aging","volume":"105","author":"Ho","year":"2020","journal-title":"Haematologica"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Kandarakov, O., Belyavsky, A., and Semenova, E. (2022). Bone Marrow Niches of Hematopoietic Stem and Progenitor Cells. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23084462"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/s41586-022-04786-y","article-title":"Clonal dynamics of haematopoiesis across the human lifespan","volume":"606","author":"Mitchell","year":"2022","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/s41580-019-0103-9","article-title":"Haematopoietic stem cell activity and interactions with the niche","volume":"20","author":"Pinho","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e2319366121","DOI":"10.1073\/pnas.2319366121","article-title":"Aging and comprehensive molecular profiling in acute myeloid leukemia","volume":"121","author":"Li","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e67","DOI":"10.1016\/S2666-7568(21)00300-7","article-title":"The costs and benefits of senotherapeutics for human health","volume":"3","author":"Raffaele","year":"2022","journal-title":"Lancet Healthy Longev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1038\/s41467-024-46020-5","article-title":"The long and winding road of reprogramming-induced rejuvenation","volume":"15","author":"Gladyshev","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/s41586-022-04785-z","article-title":"The longitudinal dynamics and natural history of clonal haematopoiesis","volume":"606","author":"Fabre","year":"2022","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.3324\/haematol.2021.280021","article-title":"Clonal hematopoiesis of indeterminate potential-related epigenetic age acceleration correlates with clonal hematopoiesis of indeterminate potential clone size in patients with high morbidity","volume":"107","author":"Feldkamp","year":"2022","journal-title":"Haematologica"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3371","DOI":"10.1182\/blood-2017-01-763425","article-title":"Clinical significance of somatic mutation in unexplained blood cytopenia","volume":"129","author":"Malcovati","year":"2017","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1146\/annurev-med-042921-112347","article-title":"Clonal Hematopoiesis and Its Impact on Human Health","volume":"74","author":"Ahmad","year":"2023","journal-title":"Annu. Rev. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1056\/NEJMoa1408617","article-title":"Age-related clonal hematopoiesis associated with adverse outcomes","volume":"371","author":"Jaiswal","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1056\/NEJMoa1409405","article-title":"Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence","volume":"371","author":"Genovese","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13045-020-00864-8","article-title":"Mechanisms and rejuvenation strategies for aged hematopoietic stem cells","volume":"13","author":"Li","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1186\/s13287-021-02498-0","article-title":"EGR1 dysregulation defines an inflammatory and leukemic program in cell trajectory of human-aged hematopoietic stem cells (HSC)","volume":"12","author":"Desterke","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.cell.2012.06.023","article-title":"The origin and evolution of mutations in acute myeloid leukemia","volume":"150","author":"Welch","year":"2012","journal-title":"Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1038\/nature13619","article-title":"Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells","volume":"512","author":"Flach","year":"2014","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"114388","DOI":"10.1016\/j.celrep.2024.114388","article-title":"G2 arrest primes hematopoietic stem cells for megakaryopoiesis","volume":"43","author":"Garyn","year":"2024","journal-title":"Cell Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1038\/s41467-023-37783-4","article-title":"Restoring bone marrow niche function rejuvenates aged hematopoietic stem cells by reactivating the DNA Damage Response","volume":"14","author":"Ramalingam","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3090","DOI":"10.1016\/j.cell.2024.04.018","article-title":"An age-progressive platelet differentiation path from hematopoietic stem cells causes exacerbated thrombosis","volume":"187","author":"Poscablo","year":"2024","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1152\/physiol.00054.2024","article-title":"Metabolic Alterations in HSCs during Aging and Leukemogenesis","volume":"40","author":"Chiang","year":"2025","journal-title":"Physiology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1186\/s12964-024-01663-1","article-title":"Molecular mechanisms of aging and anti-aging strategies","volume":"22","author":"Li","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Gil, L., Pascual-Ahuir, A., and Proft, M. (2023). Genomic Instability and Epigenetic Changes during Aging. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241814279"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.stem.2017.07.010","article-title":"Therapy-Related Clonal Hematopoiesis in Patients with Non-hematologic Cancers Is Common and Associated with Adverse Clinical Outcomes","volume":"21","author":"Coombs","year":"2017","journal-title":"Cell Stem Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1016\/j.stem.2023.07.012","article-title":"Single-cell multi-omics defines the cell-type-specific impact of splicing aberrations in human hematopoietic clonal outgrowths","volume":"30","author":"Chamely","year":"2023","journal-title":"Cell Stem Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1053\/j.seminhematol.2021.12.003","article-title":"Clonal dynamics of hematopoietic stem cell compartment in aplastic anemia","volume":"59","author":"Visconte","year":"2022","journal-title":"Semin. Hematol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1186\/s12967-024-05900-6","article-title":"Cellular crosstalk in the bone marrow niche","volume":"22","author":"Huang","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s13062-023-00394-6","article-title":"Aged mesenchymal stem cells and inflammation: From pathology to potential therapeutic strategies","volume":"18","author":"Yang","year":"2023","journal-title":"Biol. Direct"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12979-025-00517-9","article-title":"Differential effects of young and old hematopoietic stem cell niches on bone marrow-derived dendritic cells","volume":"22","author":"Kjuder","year":"2025","journal-title":"Immun. Ageing"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Fan, Y., Elkhalek, M., Zhang, Y., Liu, L., Tian, Q., Chueakula, N., Ramasamy, S.K., Dalan, R., Habib, S.J., and Kusumbe, A.P. (2025). Bone marrow adipocytes: Key players in vascular niches, aging, and disease. Front. Cell Dev. Biol., 13.","DOI":"10.3389\/fcell.2025.1633801"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/s44161-024-00482-4","article-title":"Systemic and local regulation of hematopoietic homeostasis in health and disease","volume":"3","author":"Carpenter","year":"2024","journal-title":"Nat. Cardiovasc. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e2412317122","DOI":"10.1073\/pnas.2412317122","article-title":"Periarteriolar niches become inflamed in aging bone marrow, remodeling the stromal microenvironment and depleting lymphoid progenitors","volume":"122","author":"Du","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3120","DOI":"10.1016\/j.cell.2024.04.013","article-title":"Mapping the cellular biogeography of human bone marrow niches using single-cell transcriptomics and proteomic imaging","volume":"187","author":"Bandyopadhyay","year":"2024","journal-title":"Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1038\/s41375-024-02226-6","article-title":"Clonal hematopoiesis and its impact on the aging osteo-hematopoietic niche","volume":"38","author":"Winter","year":"2024","journal-title":"Leukemia"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.stem.2023.03.005","article-title":"Harnessing matrix stiffness to engineer a bone marrow niche for hematopoietic stem cell rejuvenation","volume":"30","author":"Zhang","year":"2023","journal-title":"Cell Stem Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"100009","DOI":"10.1016\/j.mbm.2023.100009","article-title":"Stiffness matters: A soft bone marrow organoid rejuvenates hematopoietic stem cells","volume":"1","author":"Zhang","year":"2023","journal-title":"Mechanobiol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4163","DOI":"10.1172\/JCI93940","article-title":"Endothelial transplantation rejuvenates aged hematopoietic stem cell function","volume":"127","author":"Poulos","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12979-023-00403-2","article-title":"An aging-related immune landscape in the hematopoietic immune system","volume":"21","author":"Lv","year":"2024","journal-title":"Immun. Ageing"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"qiaf117","DOI":"10.1093\/jleuko\/qiaf117","article-title":"The complex role of neutrophils in healthy aging, inflammaging, and frailty","volume":"117","author":"Abdullah","year":"2025","journal-title":"J. Leukoc. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/imr.13153","article-title":"Neutrophils in aging and aging-related pathologies","volume":"314","author":"Strecker","year":"2023","journal-title":"Immunol. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1038\/s41392-025-02371-z","article-title":"Immunosenescence: Signaling pathways, diseases and therapeutic targets","volume":"10","author":"Fu","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s12979-025-00534-8","article-title":"Phenotypes, mechanisms, and therapeutic strategies of natural killer cell immunosenescence","volume":"22","author":"Guo","year":"2025","journal-title":"Immun. Ageing"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Brauning, A., Rae, M., Zhu, G., Fulton, E., Admasu, T.D., Stolzing, A., and Sharma, A. (2022). Aging of the Immune System: Focus on Natural Killer Cells Phenotype and Functions. Cells, 11.","DOI":"10.3390\/cells11061017"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3292","DOI":"10.1038\/s41467-023-38810-0","article-title":"Age-associated B cells predict impaired humoral immunity after COVID-19 vaccination in patients receiving immune checkpoint blockade","volume":"14","author":"Hosseini","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Yu, Y., Lu, C., Yu, W., Lei, Y., Sun, S., Liu, P., Bai, F., Chen, Y., and Chen, J. (2024). B Cells Dynamic in Aging and the Implications of Nutritional Regulation. Nutrients, 16.","DOI":"10.3390\/nu16040487"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e13671","DOI":"10.1111\/acel.13671","article-title":"Age-related thymic involution: Mechanisms and functional impact","volume":"21","author":"Liang","year":"2022","journal-title":"Aging Cell"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Mold, J.E., R\u00e9u, P., Olin, A., Bernard, S., Micha\u00eblsson, J., Rane, S., Yates, A., Khosravi, A., Salehpour, M., and Possnert, G. (2019). Cell generation dynamics underlying naive T-cell homeostasis in adult humans. PLoS Biol., 17.","DOI":"10.1101\/635995"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1182\/blood.2023023105","article-title":"IL-1 in aging and pathologies of hematopoietic stem cells","volume":"144","author":"Caiado","year":"2024","journal-title":"Blood"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Remigante, A., Spinelli, S., Basile, N., Caruso, D., Falliti, G., Dossena, S., Marino, A., and Morabito, R. (2022). Oxidation Stress as a Mechanism of Aging in Human Erythrocytes: Protective Effect of Quercetin. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147781"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"105504","DOI":"10.1016\/j.archger.2024.105504","article-title":"Elevated mtDNA content in RBCs promotes oxidative stress may be responsible for faster senescence in men","volume":"125","author":"Zhou","year":"2024","journal-title":"Arch. Gerontol. Geriatr."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Kyriacou, R.P., and Shibeeb, S. (2025). Red Blood Cells and Human Aging: Exploring Their Biomarker Potential. Diagnostics, 15.","DOI":"10.3390\/diagnostics15161993"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1038\/s12276-025-01480-7","article-title":"Hallmarks of cellular senescence: Biology, mechanisms, regulations","volume":"57","author":"Ajoolabady","year":"2025","journal-title":"Exp. Mol. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2842","DOI":"10.1182\/blood-2015-05-645424","article-title":"Neutrophil oxidative burst activates ATM to regulate cytokine production and apoptosis","volume":"126","author":"Harbort","year":"2015","journal-title":"Blood"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"338","DOI":"10.52601\/bpr.2023.230032","article-title":"Regulation of cellular senescence by innate immunity","volume":"9","author":"Hou","year":"2023","journal-title":"Biophys. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"442","DOI":"10.37349\/ei.2023.00112","article-title":"Mitochondrial dysfunction at the cornerstone of inflammatory exacerbation in aged macrophages","volume":"3","author":"Maurmann","year":"2023","journal-title":"Explor. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e13622","DOI":"10.1111\/acel.13622","article-title":"Defective mitophagy in aged macrophages promotes mitochondrial DNA cytosolic leakage to activate STING signaling during liver sterile inflammation","volume":"21","author":"Zhong","year":"2022","journal-title":"Aging Cell"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"9234","DOI":"10.18632\/aging.102438","article-title":"Age-associated changes in human CD4(+) T cells point to mitochondrial dysfunction consequent to impaired autophagy","volume":"11","author":"Bektas","year":"2019","journal-title":"Aging"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Chen, Y., Ye, Y., Krau\u00df, P.L., L\u00f6we, P., Pfeiffenberger, M., Damerau, A., Ehlers, L., Buttgereit, T., Hoff, P., and Buttgereit, F. (2022). Age-related increase of mitochondrial content in human memory CD4+ T cells contributes to ROS-mediated increased expression of proinflammatory cytokines. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.911050"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12979-019-0153-z","article-title":"Topological DNA damage, telomere attrition and T cell senescence during chronic viral infections","volume":"16","author":"Ji","year":"2019","journal-title":"Immun. Ageing"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1182\/blood.2019000200","article-title":"TNF-\u03b1-driven inflammation and mitochondrial dysfunction define the platelet hyperreactivity of aging","volume":"134","author":"McMahon","year":"2019","journal-title":"Blood"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"220","DOI":"10.3324\/haematol.2019.240440","article-title":"Desialylation of O-glycans on glycoprotein Ib\u03b1 drives receptor signaling and platelet clearance","volume":"106","author":"Wang","year":"2021","journal-title":"Haematologica"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"eabd6737","DOI":"10.1126\/scitranslmed.abd6737","article-title":"Repurposed drugs block toxin-driven platelet clearance by the hepatic Ashwell-Morell receptor to clear Staphylococcus aureus bacteremia","volume":"13","author":"Sun","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1161\/CIRCRESAHA.123.322914","article-title":"Mitofusin-2 Regulates Platelet Mitochondria and Function","volume":"134","author":"Jacob","year":"2024","journal-title":"Circ. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.thromres.2022.12.004","article-title":"Platelet ageing: A review","volume":"231","author":"Allan","year":"2023","journal-title":"Thromb. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.thromres.2022.01.013","article-title":"Longitudinal multiparametric characterization of platelet dysfunction in COVID-19: Effects of disease severity, anticoagulation therapy and inflammatory status","volume":"211","author":"Martyanov","year":"2022","journal-title":"Thromb. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1038\/s41467-021-22053-y","article-title":"Mutant ASXL1 induces age-related expansion of phenotypic hematopoietic stem cells through activation of Akt\/mTOR pathway","volume":"12","author":"Fujino","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"7966","DOI":"10.1038\/s41467-024-52318-1","article-title":"Aging is associated with functional and molecular changes in distinct hematopoietic stem cell subsets","volume":"15","author":"Su","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1038\/s41375-025-02657-9","article-title":"The role of ASXL1, SRSF2, and EZH2 mutations in chromatin dysregulation of myelodysplastic neoplasia and acute myeloid leukemia","volume":"39","author":"Yu","year":"2025","journal-title":"Leukemia"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Lim, K., Kan, W.L., Nair, P.C., Kutyna, M., Lopez, A.F., Hercus, T., Ross, D.M., Lane, S., Fong, C.Y., and Brown, A. (2024). CBL mutations in chronic myelomonocytic leukemia often occur in the RING domain with multiple subclones per patient: Implications for targeting. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0310641"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.molcel.2020.04.008","article-title":"Single-Cell Analyses Reveal Megakaryocyte-Biased Hematopoiesis in Myelofibrosis and Identify Mutant Clone-Specific Targets","volume":"78","author":"Psaila","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1186\/s13045-020-00994-z","article-title":"Molecular and cellular mechanisms of aging in hematopoietic stem cells and their niches","volume":"13","author":"Zhang","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1158\/2159-8290.CD-18-1474","article-title":"Aging Human Hematopoietic Stem Cells Manifest Profound Epigenetic Reprogramming of Enhancers That May Predispose to Leukemia","volume":"9","author":"Adelman","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_81","first-page":"1590","article-title":"Clonal hematopoiesis: Mechanisms driving dominance of stem cell clones","volume":"136","author":"Challen","year":"2020","journal-title":"Blood"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"131","DOI":"10.2147\/OTT.S145971","article-title":"Targeting histone methyltransferase and demethylase in acute myeloid leukemia therapy","volume":"11","author":"Castelli","year":"2018","journal-title":"OncoTargets Ther."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"5089","DOI":"10.1158\/0008-5472.CAN-20-3761","article-title":"TET2 and DNMT3A Mutations Exert Divergent Effects on DNA Repair and Sensitivity of Leukemia Cells to PARP Inhibitors","volume":"81","author":"Maifrede","year":"2021","journal-title":"Cancer Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1016\/j.ccell.2022.10.004","article-title":"The m(6)A reader IGF2BP2 regulates glutamine metabolism and represents a therapeutic target in acute myeloid leukemia","volume":"40","author":"Weng","year":"2022","journal-title":"Cancer Cell"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1038\/s41556-025-01709-7","article-title":"Differentiation, ageing and leukaemia alter the metabolic profile of human bone marrow haematopoietic stem and progenitor cells","volume":"27","author":"Lalioti","year":"2025","journal-title":"Nat. Cell Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1186\/s13287-025-04304-7","article-title":"Mitochondrial quality control in hematopoietic stem cells: Mechanisms, implications, and therapeutic opportunities","volume":"16","author":"Liao","year":"2025","journal-title":"Stem Cell Res. Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1158\/0008-5472.CAN-23-1006","article-title":"Oxidative Phosphorylation Fueled by Fatty Acid Oxidation Sensitizes Leukemic Stem Cells to Cold","volume":"83","author":"Griessinger","year":"2023","journal-title":"Cancer Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e220008","DOI":"10.20900\/immunometab20220008","article-title":"CD36-Mediated Fatty Acid Oxidation in Hematopoietic Stem Cells Is a Novel Mechanism of Emergency Hematopoiesis in Response to Infection","volume":"4","author":"Maryanovich","year":"2022","journal-title":"Immunometabolism"},{"key":"ref_89","unstructured":"Ni\u00f1o, K.E., Adema, V., Gray, A.E., Cowan, C.M., Schleicher, W.E., Hosseini, M., Bennett, S.N., Patel, S.B., Moreira, S., and Danis, E. (2026). Aberrant oxidative metabolism selects for TET2-deficient hematopoietic stem and progenitor cells. bioRxiv."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Kouroukli, O., Symeonidis, A., Foukas, P., Maragkou, M.K., and Kourea, E.P. (2022). Bone Marrow Immune Microenvironment in Myelodysplastic Syndromes. Cancers, 14.","DOI":"10.3390\/cancers14225656"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e895","DOI":"10.1097\/HS9.0000000000000895","article-title":"Unraveling Heterogeneity in the Aging Hematopoietic Stem Cell Compartment: An Insight From Single-cell Approaches","volume":"7","author":"Yang","year":"2023","journal-title":"Hemasphere"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1038\/s43587-024-00694-0","article-title":"Aged bone marrow macrophages drive systemic aging and age-related dysfunction via extracellular vesicle-mediated induction of paracrine senescence","volume":"4","author":"Hou","year":"2024","journal-title":"Nat. Aging"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1038\/s41423-023-01072-3","article-title":"Aged hematopoietic stem cells entrap regulatory T cells to create a prosurvival microenvironment","volume":"20","author":"Liao","year":"2023","journal-title":"Cell. Mol. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s00432-025-06244-4","article-title":"Mesenchymal stem cells in the bone marrow microenvironment: A double-edged sword for AML","volume":"151","author":"Saadh","year":"2025","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1186\/s12964-023-01231-z","article-title":"Abnormal adipogenic signaling in the bone marrow mesenchymal stem cells contributes to supportive microenvironment for leukemia development","volume":"21","author":"Sabbah","year":"2023","journal-title":"Cell Commun. Signal."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e70132","DOI":"10.1002\/hem3.70132","article-title":"Age-stratified machine learning identifies divergent prognostic significance of molecular alterations in AML","volume":"9","author":"Eckardt","year":"2025","journal-title":"Hemasphere"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3546","DOI":"10.1182\/blood.2021014520","article-title":"Impact of diagnostic genetics on remission MRD and transplantation outcomes in older patients with AML","volume":"139","author":"Murdock","year":"2022","journal-title":"Blood"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"4084","DOI":"10.1200\/JCO.23.02631","article-title":"Risk Stratification in Older Intensively Treated Patients With AML","volume":"42","author":"Versluis","year":"2024","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"102549","DOI":"10.1016\/j.eclinm.2024.102549","article-title":"Survival of adult AML patients treated with chemotherapy in the U.S. population by age, race and ethnicity, sex, calendar-year period, and AML subgroup, 2001\u20132019","volume":"71","author":"Linet","year":"2024","journal-title":"EClinicalMedicine"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Ansarian, M.A., Fatahichegeni, M., Ren, J., and Wang, X. (2025). Sex and Gender in Myeloid and Lymphoblastic Leukemias and Multiple Myeloma: From Molecular Mechanisms to Clinical Outcomes. Curr. Oncol., 32.","DOI":"10.3390\/curroncol32040204"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Rossi, G., Borlenghi, E., Zappasodi, P., Lussana, F., Bernardi, M., Basilico, C., Molteni, A., Lotesoriere, I., Turrini, M., and Frigeni, M. (2024). Adapting the Fitness Criteria for Non-Intensive Treatments in Older Patients with Acute Myeloid Leukemia to the Use of Venetoclax-Hypomethylating Agents Combination-Practical Considerations from the Real-Life Experience of the Hematologists of the Rete Ematologica Lombarda. Cancers, 16.","DOI":"10.3390\/cancers16020386"},{"key":"ref_102","first-page":"115","article-title":"Outcomes after intensive chemotherapy for secondary and myeloid-related changes acute myeloid leukemia patients aged 60 to 75 years old: A retrospective analysis from the PETHEMA registry","volume":"109","author":"Gil","year":"2024","journal-title":"Haematologica"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/s41375-021-01425-9","article-title":"Long-term survival after intensive chemotherapy or hypomethylating agents in AML patients aged 70 years and older: A large patient data set study from European registries","volume":"36","author":"Bertoli","year":"2022","journal-title":"Leukemia"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1056\/NEJMoa2012971","article-title":"Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia","volume":"383","author":"DiNardo","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1182\/blood.2020004856","article-title":"Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: A phase 3 randomized placebo-controlled trial","volume":"135","author":"Wei","year":"2020","journal-title":"Blood"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1186\/s13045-022-01361-w","article-title":"Efficacy and safety of CPX-351 versus 7\u2009+\u20093 chemotherapy by European LeukemiaNet 2017 risk subgroups in older adults with newly diagnosed, high-risk\/secondary AML: Post hoc analysis of a randomized, phase 3 trial","volume":"15","author":"Cortes","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1007\/s40265-025-02194-w","article-title":"The Role of CPX-351 in the Acute Myeloid Leukemia Treatment Landscape: Mechanism of Action, Efficacy, and Safety","volume":"85","author":"Pagano","year":"2025","journal-title":"Drugs"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"4893","DOI":"10.1200\/JCO.22.02604","article-title":"Tolerability and Efficacy of the Anticluster of Differentiation 47 Antibody Magrolimab Combined With Azacitidine in Patients With Previously Untreated AML: Phase Ib Results","volume":"41","author":"Daver","year":"2023","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1097\/CCO.0000000000000673","article-title":"A precision medicine approach to management of acute myeloid leukemia in older adults","volume":"32","author":"Khanal","year":"2020","journal-title":"Curr. Opin. Oncol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1038\/s41467-021-22560-y","article-title":"An integrative analysis of the age-associated multi-omic landscape across cancers","volume":"12","author":"Chatsirisupachai","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1053\/j.seminhematol.2024.10.005","article-title":"RNA splicing as a therapeutic target in myelodysplastic syndromes","volume":"61","author":"Tseng","year":"2024","journal-title":"Semin. Hematol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1056\/NEJMoa1516192","article-title":"Genomic Classification and Prognosis in Acute Myeloid Leukemia","volume":"374","author":"Papaemmanuil","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"5177","DOI":"10.1182\/bloodadvances.2025016399","article-title":"Long-term results from the AGILE study of azacitidine plus ivosidenib vs. placebo in newly diagnosed IDH1-mutated AML","volume":"9","author":"Montesinos","year":"2025","journal-title":"Blood Adv."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1182\/blood.2021014586","article-title":"Phase 3 trial of gilteritinib plus azacitidine vs. azacitidine for newly diagnosed FLT3mut+ AML ineligible for intensive chemotherapy","volume":"140","author":"Wang","year":"2022","journal-title":"Blood"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.ccell.2019.08.005","article-title":"Mitochondrial Reprogramming Underlies Resistance to BCL-2 Inhibition in Lymphoid Malignancies","volume":"36","author":"Liu","year":"2019","journal-title":"Cancer Cell"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s13045-025-01735-w","article-title":"Immunosenescence and cancer: Molecular hallmarks, tumor microenvironment remodeling, and age-specific immunotherapy challenges","volume":"18","author":"Liu","year":"2025","journal-title":"J. Hematol. Oncol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.cpt.2023.08.001","article-title":"Impact of immunosenescence and inflammaging on the effects of immune checkpoint inhibitors","volume":"2","author":"Hou","year":"2024","journal-title":"Cancer Pathog. Ther."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1007\/s10522-024-10114-w","article-title":"Inhibitory immune checkpoints suppress the surveillance of senescent cells promoting their accumulation with aging and in age-related diseases","volume":"25","author":"Salminen","year":"2024","journal-title":"Biogerontology"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"3861","DOI":"10.21037\/tlcr-2025-640","article-title":"Real-world outcomes and association between immune-related adverse events and therapeutic efficacy of nivolumab plus ipilimumab in elderly patients (\u226575 years) with advanced non-small cell lung cancer","volume":"14","author":"Minami","year":"2025","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1186\/s12964-025-02082-6","article-title":"Immunosenescence promotes cancer development: From mechanisms to treatment strategies","volume":"23","author":"Wang","year":"2025","journal-title":"Cell Commun. Signal."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s13148-023-01496-8","article-title":"Time to relapse in chronic lymphocytic leukemia and DNA-methylation-based biological age","volume":"15","author":"Nannini","year":"2023","journal-title":"Clin. Epigenet."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"e14100","DOI":"10.1111\/acel.14100","article-title":"Aging clock based on nucleosome reorganisation derived from cell-free DNA","volume":"23","author":"Shtumpf","year":"2024","journal-title":"Aging Cell"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1080\/17501911.2024.2340958","article-title":"Cell-free DNA methylation patterns in aging and their association with inflamm-aging","volume":"16","author":"Li","year":"2024","journal-title":"Epigenomics"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"13452","DOI":"10.18632\/aging.206184","article-title":"Cell-type specific epigenetic clocks to quantify biological age at cell-type resolution","volume":"16","author":"Tong","year":"2024","journal-title":"Aging"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s13059-024-03269-9","article-title":"Breaking down causes, consequences, and mediating effects of telomere length variation on human health","volume":"25","author":"Moix","year":"2024","journal-title":"Genome Biol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.stem.2024.05.010","article-title":"Selective advantage of mutant stem cells in human clonal hematopoiesis is associated with attenuated response to inflammation and aging","volume":"31","author":"Jakobsen","year":"2024","journal-title":"Cell Stem Cell"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/s41577-023-00843-3","article-title":"Clonal haematopoiesis and dysregulation of the immune system","volume":"23","author":"Belizaire","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Morganti, C., and Ito, K. (2021). Mitochondrial Contributions to Hematopoietic Stem Cell Aging. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222011117"},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Goyani, P., Christodoulou, R., and Vassiliou, E. (2024). Immunosenescence: Aging and Immune System Decline. Vaccines, 12.","DOI":"10.3390\/vaccines12121314"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"e13767","DOI":"10.1111\/acel.13767","article-title":"Senolytic drugs, dasatinib and quercetin, attenuate adipose tissue inflammation, and ameliorate metabolic function in old age","volume":"22","author":"Islam","year":"2023","journal-title":"Aging Cell"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1007\/s11357-023-00830-5","article-title":"Long-term dasatinib plus quercetin effects on aging outcomes and inflammation in nonhuman primates: Implications for senolytic clinical trial design","volume":"45","author":"Ruggiero","year":"2023","journal-title":"Geroscience"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/nm.4010","article-title":"Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice","volume":"22","author":"Chang","year":"2016","journal-title":"Nat. Med."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1186\/s13287-022-02901-4","article-title":"Clearance of senescent cells with ABT-263 improves biological functions of synovial mesenchymal stem cells from osteoarthritis patients","volume":"13","author":"Miura","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/s41586-020-2403-9","article-title":"Senolytic CAR T cells reverse senescence-associated pathologies","volume":"583","author":"Amor","year":"2020","journal-title":"Nature"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1038\/s43587-024-00670-8","article-title":"An NAD(+)-dependent metabolic checkpoint regulates hematopoietic stem cell activation and aging","volume":"4","author":"Song","year":"2024","journal-title":"Nat. Aging"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Ibneeva, L., Singh, S.P., Sinha, A., Eski, S.E., Wehner, R., Rupp, L., Kovtun, I., P\u00e9rez-Valencia, J.A., Gerbaulet, A., and Reinhardt, S. (2024). CD38 promotes hematopoietic stem cell dormancy. PLoS Biol., 22.","DOI":"10.1371\/journal.pbio.3002517"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1007\/s11357-023-00752-2","article-title":"Boosting NAD ameliorates hematopoietic impairment linked to short telomeres in vivo","volume":"45","author":"Stock","year":"2023","journal-title":"Geroscience"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"ra75","DOI":"10.1126\/scisignal.2000559","article-title":"mTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells","volume":"2","author":"Chen","year":"2009","journal-title":"Sci. Signal."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1038\/s41467-020-20801-0","article-title":"Niche derived netrin-1 regulates hematopoietic stem cell dormancy via its receptor neogenin-1","volume":"12","author":"Renders","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"112304","DOI":"10.1016\/j.celrep.2023.112304","article-title":"Temporal multimodal single-cell profiling of native hematopoiesis illuminates altered differentiation trajectories with age","volume":"42","author":"Dhapola","year":"2023","journal-title":"Cell Rep."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"e112348","DOI":"10.15252\/embj.2022112348","article-title":"Bidirectional interplay between metabolism and epigenetics in hematopoietic stem cells and leukemia","volume":"42","author":"Zhang","year":"2023","journal-title":"EMBO J."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1007\/s11357-024-01360-4","article-title":"DNA methylation drives hematopoietic stem cell aging phenotypes after proliferative stress","volume":"47","author":"Yanai","year":"2025","journal-title":"Geroscience"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"7858","DOI":"10.1038\/s41467-024-52302-9","article-title":"Long-term longitudinal analysis of 4187 participants reveals insights into determinants of clonal hematopoiesis","volume":"15","author":"Uddin","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"3771","DOI":"10.1182\/bloodadvances.2024013228","article-title":"Clonal hematopoiesis of indeterminate potential as a prognostic factor: A systematic review and meta-analysis","volume":"8","author":"Singh","year":"2024","journal-title":"Blood Adv."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"EVIDoa2200310","DOI":"10.1056\/EVIDoa2200310","article-title":"Prediction of risk for myeloid malignancy in clonal hematopoiesis","volume":"2","author":"Weeks","year":"2023","journal-title":"NEJM Evid."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/s41586-022-05448-9","article-title":"Common and rare variant associations with clonal haematopoiesis phenotypes","volume":"612","author":"Kessler","year":"2022","journal-title":"Nature"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"39821","DOI":"10.1038\/s41598-025-23468-z","article-title":"Acute myeloid leukemia risk stratification in younger and older patients through transcriptomic machine learning models","volume":"15","author":"Silva","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"26417","DOI":"10.18632\/oncotarget.25443","article-title":"Distinct age-associated molecular profiles in acute myeloid leukemia defined by comprehensive clinical genomic profiling","volume":"9","author":"Tarlock","year":"2018","journal-title":"Oncotarget"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.clml.2024.12.020","article-title":"Prognostic Value of Dynamic Measurable Residual Disease Monitoring by Multiflowcytometry in Elderly Patients with Nonintensively Treated Acute Myeloid Leukemia","volume":"25","author":"Sun","year":"2025","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1016\/j.stem.2024.04.020","article-title":"Autophagy counters inflammation-driven glycolytic impairment in aging hematopoietic stem cells","volume":"31","author":"Dellorusso","year":"2024","journal-title":"Cell Stem Cell"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jgo.2020.07.003","article-title":"Implementation of geriatric assessment in oncology settings: A systematic realist review","volume":"12","author":"McKenzie","year":"2021","journal-title":"J. Geriatr. Oncol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.beha.2019.05.007","article-title":"Clonal Hematopoiesis and risk of Acute Myeloid Leukemia","volume":"32","author":"Desai","year":"2019","journal-title":"Best. Pract. Res. Clin. Haematol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1001\/jama.2023.1946","article-title":"Diagnosis and Treatment of Chronic Lymphocytic Leukemia: A Review","volume":"329","author":"Shadman","year":"2023","journal-title":"JAMA"},{"key":"ref_154","first-page":"273","article-title":"Therapy-induced senescent tumor cells in cancer relapse","volume":"3","author":"Song","year":"2023","journal-title":"J. Natl. Cancer Cent."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1001\/jamaoncol.2025.3601","article-title":"Emerging Artificial Intelligence Technologies for Risk Assessment and Management in Acute Myeloid Leukemia: A Review","volume":"11","author":"Ansarian","year":"2025","journal-title":"JAMA Oncol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"eaan4673","DOI":"10.1126\/science.aan4673","article-title":"Clonal hematopoiesis in human aging and disease","volume":"366","author":"Jaiswal","year":"2019","journal-title":"Science"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s00018-022-04356-5","article-title":"Mechanisms involved in hematopoietic stem cell aging","volume":"79","author":"Fujino","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"5449","DOI":"10.1007\/s11357-025-01594-w","article-title":"Systemic deficits in lipid homeostasis promote aging-associated impairments in B cell progenitor development","volume":"47","author":"Vicenzi","year":"2025","journal-title":"Geroscience"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/j.stem.2025.06.004","article-title":"Hallmarks of stem cell aging","volume":"32","author":"Rando","year":"2025","journal-title":"Cell Stem Cell"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1038\/s43587-023-00473-3","article-title":"Induction of mitochondrial recycling reverts age-associated decline of the hematopoietic and immune systems","volume":"3","author":"Girotra","year":"2023","journal-title":"Nat. Aging"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/9\/4043\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T04:20:03Z","timestamp":1778386803000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/9\/4043"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,30]]},"references-count":160,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27094043"],"URL":"https:\/\/doi.org\/10.3390\/ijms27094043","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,30]]}}}